Systematic analysis of fatty acid desaturases in breast invasive carcinoma: The prognosis, gene mutation, and tumor immune microenvironment

Breast invasive carcinoma (BRCA) is one of the most common cancers in women, with its malignant progression significantly influenced by intracellular fatty acid (FA) desaturation. Stearoyl-coenzyme A desaturase (SCD) and fatty acid desaturase 2 (FADS2) are two key rate-limiting enzymes that catalyze the FA desaturation process and cooperate to accelerate lipid metabolic activities. In this study, we investigated the potential functions of SCD and FADS2 in BRCA using bioinformatic analysis and experimental validation. The gene expression profiling interactive analysis database showed that the expression of SCD or FADS2 genes was positively linked to worse overall survival and disease-free survival in the Cancer Genome Atlas database-BRCA. The University of Alabama at Birmingham cancer data analysis portal database indicates that the expression and methylation levels of SCD or FADS2 are associated with various clinicopathological factors in patients with BRCA. Moreover, the tumor immune estimation resource and TISCH databases showed a significant positive correlation between the expression of SCD and the abundance of CD8+ T cells and macrophage cell infiltration, while the expression of FADS2 was positively correlated with the abundance of B cells. Meanwhile, SCD or FADS2 had a higher expression in monocytes/macrophages analyzed the BRCA_GSE143423 and BRCA_GSE114727_inDrop datasets. Mechanistically, the Search Tool for the Retrieval of Distant Genes and CancerSEA databases showed that SCD and FADS2 were upregulated in several cell biology signaling pathways, particularly in inflammation, apoptosis, and DNA repair. Finally, SCD or FADS2 knockdown inhibited the proliferation of MCF-7 and MDA-MB-231 cells. In summary, SCD and FADS2 play significant roles in BRCA development, suggesting that they may serve as potential therapeutic targets for BRCA treatment.


Introduction
[3] Although chemotherapy, radiotherapy, endocrinology, and immunotherapy have reduced the mortality of patients with BRCA, effective therapeutic strategies are still limited. [4,5]In the 1980s, Ookhtens et al found that almost all 14 C labeled esterified fatty acids (FAs) are originated from de novo FA synthesis in Ehrlich ascites tumor cells. [6]9] FA desaturation is the final step in de novo FA synthesis and is at the center of tumor lipid metabolism.To maintain high proliferation, tumor cells need to meet the exuberant lipid demand by synthesizing saturated fatty acids (SFA) and then modify the rigidity of SFA on the cell membrane by converting SFA to monounsaturated fatty acid (MUFA) or polyunsaturated fatty acid. [10]In addition, MUFA and polyunsaturated fatty acid are also important messengers in intercellular signaling. [11]onversely, accumulation of SFA in cells can cause lipotoxicity in cells and accelerate tumor death. [12,13]Therefore, FA desaturation is closely related to tumor occurrence and development and is the key to determining the fate of tumors. [14]tearoyl-CoA desaturase (SCD), an enzyme involved in FA desaturation, is crucial for regulating the SFA/MUFA ratio and has been identified as an important regulator of cancer cell survival and progression. [15]Many malignancies, including cancer stem cells and invasive cells, have been reported to exhibit high levels of SCD.Our previous study also demonstrated that SCD was correlated with poor prognosis in BRCA patients, and targeting SCD may be a novel therapeutic strategy for BRCA treatment. [16]However, in 2019, Kim Vriens et al found that SCD inhibition led to the activation of its desaturating isoenzyme fatty acid desaturase 2 (FADS2), which continued to produce MUFAs and promote tumor growth. [17]20] Increasing evidence suggests that inhibiting FADS2 activity can suppress the growth of various cancers, including melanoma, [21] lung cancer, [22] and ovarian cancer. [23]Furthermore, FADS2 promotes the occurrence and development of breast cancer cells by regulating the epithelial-mesenchymal transition process. [24]emarkably, knockdown of SCD or FADS2 enhanced the sensitivity of lung cancer and ovarian cancer cells to ferroptosis, which is a type of iron-dependent cell death that provides novel avenues for clinical intervention. [22,23]n this study, we employed multiple bioinformatic methods to explore the relationship between SCD or FADS2 expression and various factors in BRCA, including prognostic value, pathological stages, clinicopathological characteristics, genetic alterations, functional states at the single-cell level, and immune infiltration.Our findings offer new insights into the roles of FA desaturation in BRCA, connect the expression of 2 key desaturases with the BRCA tumor microenvironment (TME), and highlight them as potential therapeutic targets for BRCA treatment.

Gene expression profiling interactive analysis
Gene expression profiling interactive analysis (GEPIA, http:// gepia.cancer-pku.cn/)consists of RNA sequencing expression data of 9736 tumors and 8587 normal samples derived from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression databases. [25]In this study, GEPIA singlegene analysis was used to analyze the prognosis of SCD or FADS2.The prognostic values of cancer patients, including overall survival (OS) and disease-free survival (DFS), and survival curves were estimated using the Kaplan-Meier method.Hazard ratios (HR) with 95% confidence intervals are shown in the survival plot, and P < 0.05 was considered statistically significant.

PrognoScan
PrognoScan (http://dna00.bio.kyutech.ac.jp/PrognoScan/) is a widely used online database for meta-analysis of the prognostic significance of genes. [26]In this study, PrognoScan was used to analyze the association between SCD or FADS2 expression and survival in patients with breast cancer.

The Tumor Immune Estimation Resource
The Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/) is a database for the comprehensive analysis of tumor-infiltrating immune cells, [27] which consists of 10897 samples of 32 cancer types from the TCGA database.In this study, the TIMER database was used to analyze the difference SCD or FADS2 expression between tumor and normal tissues, and to evaluate the correlation between gene expression and abundance of immune infiltrates.It contains 6 immune infiltrates (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells) and various gene markers.Gene expression levels were assessed using log 2 TPM.

TISIDB
TISIDB (http://cis.hku.hk/TISIDB/index.php/) is a database that integrates many heterogeneous data sources to assess interactions between tumors and the immune system. [28]In this study, we explored the relationship between SCD or FADS2 expression and molecular subtypes using pan-cancer analysis, especially in BRCA.

The University of Alabama at the Birmingham Cancer Data Analysis Portal
The University of Alabama at the Birmingham Cancer Data Analysis Portal (UALCAN) (http://ualcan.path.uab.edu/) is a comprehensive web portal for analyzing TCGA data. [29]In this study, the expression and promoter methylation levels of SCD and FADS2 in BRCA were analyzed based on sample type, sex, age, race, nodal metastasis status, histological subtypes, major subclasses, menopause status, and individual cancer stages.The t-test was used for analysis, and P < 0.05.

cBioPortal
The cBio Cancer Genomics Portal (cBioPortal, http://www.cbioportal.org/)provides data on 10967 tumor samples from 20 cancer studies. [30,31]The samples contained gene mutations, copy number alterations, mRNA expression z-scores, and protein expression z-scores.In our study, the genomic profiles (1084 samples) included genetic alterations, co-expression, and network modulation from the genomic identification of significant targets in cancer, and SCD or FADS2 mRNA expression z-scores relative to all samples with a threshold of ± 2.0.

The tumor immune single-cell hub
The tumor immune single-cell hub (TISCH, http://tisch.comp-genomics.org/) is a single-cell RNA sequencing database focusing on the TME, [32] which can provide detailed cell-type annotation at the single-cell level, enabling exploration of the TME across a diverse range of cancers.We used datasets from BRCA_GSE143423 and BRCA_GSE143423 to analyze SCD or FADS2 expression in BRCA as a single-cell subset.

The Search Tool for the Retrieval of Distant Genes Database
The Search Tool for the Retrieval of Distant Genes Database (STRING, https://string-db.org/)compiles, assesses, and combines publicly available protein-protein interaction (PPI) data and augments them with computational forecasts of potential functions.This study submitted variously expressed SCD or FADS2-related genes to STRING to obtain information about the top 20 related PPI networks and visualize the protein-protein interactive network. [33]9.CancerSEA CancerSEA (http://biocc.hrbmu.edu.cn/CancerSEA/) was created to decode Pearson correlations between 14 different single-cell functional states and relevant genes in human malignancies.[34] In this study, we used CancerSEA to investigate the relationships between SCD or FADS2 functional states and invasive breast carcinoma at the single-cell level.

Cell culture
MCF-7 and MDA-MB-231 cells were obtained from the Cell Bank of the Shanghai Institute for Biological Sciences, Chinese Academy of Sciences.MCF-7 and MDA-MB-231 cells were cultured in Dulbecco modified Eagle medium (Sigma, St. Louis, MO) with 10% fetal bovine serum (HyClone, Logan, UT), 100 U/mL penicillin, and 100 mg/mL streptomycin.cells were maintained at 37 °C in a humidified environment in an incubator with 5% CO 2 .

Western blot
Cell lysis buffer for western blotting and cell lysates (Beyotime, Shanghai, China) containing protease inhibitors were used to extract proteins from cells, and the total protein concentration was determined using a BCA Protein Assay Kit (Bio-Rad, CA).Protein samples were collected for SDS-PAGE and then transferred to PVDF (Bio-Rad, CA).After blocking with 5% nonfat milk, the membranes were treated with primary antibodies (1:1000 dilution) and then secondary antibodies (1:3000 dilution).All antibodies were purchased from Cell Signaling Technology (Danvers, MA).Finally, membrane visualization was performed using an enhanced chemiluminescence system, and protein bands were detected using ChemiDOC MP (Bio-Rad, CA).The density of immunoreactive bands was quantified using ImageJ software (National Institute of Health, Bethesda, MA).

Statistical analysis
All in vitro experiments were repeated at least 3 times, and the results are presented as mean ± standard deviation.Student t test was used to test for statistical significance.Data were analyzed using GraphPad Prism 7.0 (GraphPad Software, San Diego, CA).P < 0.05 was considered statistically significant.

Expression of FA desaturase genes are associated with BRCA molecular subtypes
[37] To further determine the relationship between SCD or FADS2 expression and tumor molecular subtypes, we assessed the association between SCD (Fig. 2A, Fig. S1, Supplemental Digital Content, http://links.lww.com/MD/M965) or FADS2 (Fig. 2B, Fig. S2, Supplemental Digital Content, http://links.lww.com/MD/M966)expression and pan-tumor subtypes using the TISIDB database.The results showed that the SCD level varied significantly in colon adenocarcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, stomach adenocarcinoma, and lung squamous cell carcinoma molecular subtypes and the FADS2 level also varied significantly in esophageal  carcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, lower grade glioma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, prostate adenocarcinoma, skin cutaneous melanoma, stomach adenocarcinoma, and lung squamous cell carcinoma molecular subtypes.Based on the molecular subtype classification from the TCGA-BRCA database, SCD (P-value = 4e-33) and FADS2 (P-value = 3.79e-34) are good predictors of molecular subtypes in BRCA.Specifically, SCD was highly expressed in Her2 positive, luminal A, and luminal B subtypes (Fig. 2C), while FADS2 was highly expressed in the basal, Her2 positive, and luminal B subtypes (Fig. 2D).The correlations between SCD or FADS2 and tumor molecular typing are detailed in Table 1.The results revealed that the expression of SCD and FADS2 are related to the molecular subtypes of tumors, especially in BRCA.

Expression of FA desaturase genes correlated with clinicopathological characteristics in BRCA
Next, we investigated the correlation between SCD or FADS2 expression and various clinicopathological characteristics based on UALCAN analysis in BRCA samples.The results showed that SCD was significantly upregulated in BRCA patients aged 80-100 years (Fig. 3A), in individuals with stage 4 cancer (Fig. 3B), and in the Asian race (Fig. 3C).It was downregulated in nodal metastasis status (Fig. 3D), histological subtypes (Fig. 3E), and menopausal status (Fig. 3F).Additionally, FADS2 was remarkably upregulated across a wide range of BRCA patient characteristics, including age (21-100 years), all cancer stages (1-4), races (Caucasian, African-American, and Asian), nodal metastasis status (N0-3), histological subtypes (IDC, other, mucinous, metaplastic, and medullary), and menopausal status (premenopause, peri-menopause, and postmenopause) (Fig. 3G-L).Taken together, these results suggest a close correlation between SCD or FADS2 expression and clinicopathological characteristics in BRCA.These enzymes could serve as diagnostic tumor markers for BRCA, considering with different pathological parameters.Compared to FADS2, SCD is more targeted for Asian patients, aged 81-100 years, and with cancer stage 4.

Promoter methylation levels and gene mutations of FA desaturase genes in BRCA
Gene silencing and hypermethylation of tumor DNA are early molecular abnormalities in carcinogenesis.Promoter DNA methylation has been shown to affect transcriptional repression and participates in tumor oncogenesis. [38]Therefore, the promoter methylation levels of SCD or FADS2 were compared, and UALCAN analysis was performed using TCGA-BRCA samples.The results suggested that promoter methylation levels of SCD (Fig. S3A, Supplemental Digital Content, http://links.lww.com/MD/M967) and FADS2 (Fig. S3B, Supplemental Digital Content, http://links.lww.com/MD/M967) were upregulated in other age, race, individual cancer stages, nodal metastasis status, tumor history, and menopause status groups.
Furthermore, we investigated the genetic alteration characteristics of SCD and FADS2 in the TCGA-BRCA cohort using the cBioPortal network.The primary types of alterations in SCD included "deep deletion", "amplification", "structural variant", and "mutation" in patients with BRCA (Fig. 4A).For FADS2, the main alterations were "amplification", "mutation", and "multiple alterations" (Fig. 4B).The critical change in function was a mutation occurring at the active site of SCD or FADS2 desaturase, and missense or fusion mutations were the predominant mutations in SCD or FADS2 mutation.For instance, a missense mutation within the F137I domain was found in SCD patients (Fig. 4C).and the K291N domain in FADS2 (Fig. 4D) could be detected in BRCA cases.

Analysis of FA desaturase genes and immune infiltration in BRCA
Recent studies have shown that immune cell infiltration is associated with the initiation, progression, and metastasis of human cancers.To further clarify the BRCA microenvironment and the mechanism by which FA desaturase affects BRCA heterogeneity and prognosis, we investigated whether SCD or FADS2 is related to immune infiltration.The association between SCD or FADS2 expression and tumor-infiltrating immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells) in BRCA was determined using the TIMER tool.The results showed that SCD expression was positively associated with CD4+ T cells and macrophages (Fig. 5A), and FADS2 was positively correlated with B cell, neutrophil, and dendritic cell infiltration (Fig. 5B) in BRCA.We then focused on SCD (Table 2) and FADS2 (Table 3) in BRCA with the immune cell markers of B cells, T cells, CD8+ T cells, monocytes, M1 macrophages, M2 macrophages, TAM, neutrophils, natural killer cells, dendritic cells, and functional T cell markers of Th1, Th2, Tfh, Th17, Treg, and T cell exhaustion.Notably, there were significant differences in the level of immune cell infiltration between the different groups based on SCD or FADS2 (Fig. S4, Supplemental Digital Content, http://links.lww.com/MD/M968)copy numbers.In summary, the above results suggest that both SCD and FADS2 expression could affect the tumor immune microenvironment by regulating immune cell infiltration.

Single-cell expression levels of FA desaturase genes in BRCA cancer tissues
To study the potential role of FA desaturases in the immunity of BRCA, the TISCH database was used to explore SCD and FADS2 expression in the TME.As for other components of the TME, we found that SCD was mainly overexpressed in malignant tumor cells, endothelial cells, fibroblast cells, and macrophage cells, whereas it was relatively low for the immune cell components of CD4 Tconv cells, natural killer cells, B cells, and neutrophils (Fig. 6A).Meanwhile, the FADS2 expression level was mainly upregulated in malignant tumor cells, epithelial cells, mast cells, and macrophages, whereas it was extremely low in CD4 Tconv cells, Treg cells, plasma cells, and neutrophils (Fig. 6B).The distribution of SCD or FADS2 expression from each dataset is shown in Figure 6C, the UMAP plots showed that SCD and FADS2 expression levels remained higher in malignant tumor cells of the BRCA_GSE143423 dataset and macrophages and mast cells of the BRCA_GSE114727_inDrop dataset.These findings suggest that, in addition to malignant cells, SCD and FADS2 played a role in immune cells and stromal cells.

PPI network and potential functional status of FA desaturase genes
A protein interaction network is necessary for understanding the molecular mechanisms of malignancy.To explore the potential molecular mechanisms of SCD and FADS2, we conducted network analysis of FA desaturases using the STRING tool.
The results illustrated a co-expressed protein network of SCD (Fig. 7A) or FADS2 (Fig. 7B) interacting genes in the PPI networks.Among them, sterol regulatory element-binding transcription factor 1, fatty acid synthase, acetyl-CoA carboxylase alpha, and cytochrome b5 type A are common interactors of SCD and FADS2, which provides clues for further study of their functions.In addition, single-cell transcriptome sequencing is a key technique for analyzing the potential functions of candidate molecules at the single-cell level. [39]CancerSEA was used to determine whether the module is associated with carcinogenic processes in different subpopulations of BRCA cells.The results showed that SCD was correlated with inflammation and apoptosis (Fig. 7C), and FADS2 was correlated with inflammation and DNA repair (Fig. 7D).The module could promote BRCA by splicing and processing mRNA based on the clustering results of CancerSEA, and the overall expressions of SCD (Fig. 7E) and FADS2 (Fig. 7F) in BRCA were found to be heterogeneous.

Effect of FA desaturase genes on BRCA cell proliferation
To verify the efficacy of FA desaturases on BRCA cell proliferation, we used siRNA to knock down SCD or FADS2 in MCF-7 and MDA-MB-231 cells.Compared with the silencing negative control RNA interference cells, SCD or FADS2 knockdown cells showed a significant decrease in SCD or FADS2 protein expression, indicating successful knockdown (Fig. 8A and D) and the inhibition of BRCA cell proliferation was manifested (Fig. 8B  and E).Simultaneously, there was a minimal inhibitory effect on the growth of either cell line at a low dose of SCD inhibitor MF438 and FADS2 inhibitor A939572, while significant inhibiting effect on growth when using MF438 and A939572 over 50 μM (Fig. 8C and F).These results show that both SCD and FADS2 had a significant impact on BRCA cell proliferation.

Discussion
Compared with normal cells, the metabolic characteristics of cancer cells undergo significant changes, including an abnormally high demand for glucose and glutamine, de novo FA synthesis, higher lipid production, and FA uptake.De novo FA synthesis involves carboxylation, addition, desaturation, and extension of the carbon chain of acetyl-CoA.Recent studies have found that FA desaturation is closely related to tumor development and plays a crucial role in determining the fate of tumors. [14]Currently, FA desaturases include SCD and FADS2. [40]mong FA desaturases, SCD is the most widely studied, and it promotes tumor initiation, occurrence, development, metastasis, and stemness formation. [41,42]Consistent with the role of SCD in promoting tumor growth, our previous studies also found that a new SCD inhibitor could induce SCD-dependent apoptosis and autophagy in BRCA cells, which benefits breast cancer treatment. [16,43]However, recent studies have confirmed that simply inhibiting SCD in tumor cells leads to an increase in FADS2 activity and promotes tumor growth instead. [17]Therefore, it is important to explore the expression and significance of FA desaturases, represented by SCD and FADS2, in tumors and their role in the BRCA immune microenvironment, tumor diagnosis, and prognosis.
Based on multivariate analysis, SCD or FADS2 was identified as a prognostic risk factor for 33 types of cancer, especially BRCA.In addition, both SCD and FADS2 had the highest correlation with the molecular subtype of BRCA, especially Her2 positive BRCA.Further, UALCAN analysis of the correlation between SCD or FADS2 expression and patient clinicopathological parameters showed that higher SCD and FADS2 expression participated in BRCA progression.These data indicate that FA desaturation promotes BRCA development and further suggests the synergistic effect of SCD and FADS2 on BRCA progression.In the future, we will continue to explore the role of FA desaturases in tumor diagnosis and prognosis using clinical data.
Methylation of the promoter CpG island blocks binding of the transcription factor complex to the promoter, thereby inhibiting gene expression. [44]Hypermethylation often leads to transcriptional silencing of tumor suppressor genes and DNA repair genes, resulting in abnormal regulation of growth and differentiation of normal cells and failure to repair DNA damage, leading to the occurrence of tumors. [45]Further analysis of the promoter methylation level between SCD or FADS2 expression and patient clinicopathological parameters showed that SCD and FADS2 methylation were significantly related to major subclasses, patient sex, age, race, nodal metastasis status, tumor history, menopause status, and individual cancer stages.Additionally, the data suggested that the "deep deletion" type was the predominant alteration for SCD, while the "amplification" type was the main alteration for FADS2 in BRCA.In 8 BRCA cases, a missense mutation within the F137I domain in SCD and the K291N domain in FADS2 was also detected.
The functional roles of SCD and FADS2 showed that SCD is correlated with inflammation and apoptosis, whereas FADS2 is correlated with inflammation and DNA repair.The difference in cell signaling between SCD and FADS2 might be due to inherent heterogeneity in BRCA or the limited number of samples for single-cell scRNA-Seq analysis.To further investigate the potential molecular mechanisms of SCD and FADS2, the STRING database was used to predict protein-protein interactions.The results showed that sterol regulatory element-binding transcription factor 1, fatty acid synthase, acetyl-CoA carboxylase alpha, and cytochrome b5 type A were predicted to be functional partners of SCD and FADS2, which provided clues for FA metabolism cell signaling in BRCA.
During the formation and growth of the tumor, immune cells not only suppress the tumor but also shape the immunogenicity of cancer cells in the elimination, equilibrium, and escape phase. [46]Therefore, immune cells in the TME include natural killer cells, macrophages, neutrophils, B cells, and T cells, which play pivotal roles in BRCA onset, development, metastasis, and spread. [47][50] In our study, we found that SCD and FADS2 expression were significantly positively associated with macrophage cells.Therefore, SCD and FADS2 could be used as potential targets to regulate the immune microenvironment, thereby regulating the occurrence and development of tumors.
However, there are still some limitations to present study.Firstly, the animal experiments in vivo are needed to further verify the anti-proliferation effect of SCD1 or FADS2 inhibitors on the BRCA cells.Secondly, considering the promoting effect of SCD1 and FADS2 on breast cancer development, how to combine these inhibitors to promote the therapeutic effect of existing chemotherapy drugs is a question worth exploring.Finally, some omics techniques such as transcriptomics, genomics, and metabolomics are needed to investigate how SCD1or FADS2 regulates related cell signaling and metabolic change to accelerate BRCA development.

Conclusions
Overall, this study provides an in-depth understanding of the heterogeneity and complexity of the molecular biological characteristics of SCD and FADS2 by analyzing the prognosis, mutations, and tumor immune microenvironment in BRCA.We demonstrated that SCD1 and FADS2 could be potential biomarkers to predict or diagnose aggressive breast cancer, and the SCD1 or FADS2 expression is positively related to infiltration of immune cells in tumor microenvironment.

Figure 1 .
Figure 1.Prognostic analysis of SCD or FADS2 in BRCA.Overall survival analysis of SCD (A) or FADS2 (E) and disease-free survival analysis of SCD (B) or FADS2 (F) in 33 types of human cancers were determined using the GEPIA database.Overall survival analysis of SCD (C) or FADS2 (G), and disease-specific survival analysis of SCD (D) or relapse-free survival analysis of FADS2 (H) in BRCA using the PrognoScan database.

Figure 3 .
Figure 3.The SCD or FADS2 transcription in different clinical characteristics of patients in BRCA.Box plots evaluating SCD expression in BRCA among different groups of patients based on clinical parameters including patient age (A), individual cancer stages (B), patient race (C), nodal metastasis status (D), histological subtypes (E), menopause status (F), as well as FADS2 expression in BRCA patients based on patient age (G), individual cancer stages (H), patient race (I), nodal metastasis status (J), histological subtypes (K), and menopausal status (L) using the UALCAN database (*P < 0.05; **P < 0.01; ***P < 0.001).

Figure 4 .
Figure 4.The genetic alterations of SCD or FADS2 in BRCA of TCGA.Alteration summary of SCD (A) and FADS2 (B) for BRCA tumors.The sites of SCD (C) or FADS2 (D) genetic alterations using the cBioPortal online platform.

Figure 5 .
Figure 5. Correlation between SCD or FADS2 expression and immune infiltrating cells.Relationship between SCD (A) or FADS2 (B) expression levels and immune cell infiltration levels in BRCA, BRCA-basal, BRCA-Her2, and BRCA-luminal using the TIMER tool.

Table 2
Correlation analysis between stearoyl-CoA desaturase 1 and related genes and markers of immune cells in BRCA.

Table 3
Correlation analysis between fatty acid desaturase 2 and related genes and markers of immune cells in BRCA.